BACKGROUND:Nerve growth factor is a protein that induces nerve growth and regulates biological behaviors such as proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To investigate the promoting effect of nerve growth factor on chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured,and nerve growth factor was transfected into bone marrow mesenchymal stem cells by lentiviral transfection.The effects of nerve growth factor on the proliferation,migration,hypertrophic differentiation,and chondrogenic differentiation of bone marrow mesenchymal stem cells were detected by CCK-8 assay,cell scratch assay,alizarin red staining,and western blot assay,using the transfected null-loaded virus as control.To further investigate the promoting effect of nerve growth factor on the chondrogenic differentiation of bone marrow mesenchymal stem cells,interleukin 1β was added in bone marrow mesenchymal stem cells transfected with empty virus and nerve growth factor for 14 days.The expression of proteins related to chondrogenic differentiation and hypertrophic differentiation was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that nerve growth factor had no significant effect on the proliferation of bone marrow mesenchymal stem cells.(2)Compared with the control group,overexpression of nerve growth factor enhanced the migration ability of the cells,and the expression of cartilage-associated proteins type II collagen and SOX9 was up-regulated(P<0.05),while the expression of hypertrophic-associated proteins type X collagen and Runx2 was down-regulated(P<0.05).(3)Compared with the empty virus+interleukin 1β group,the expression of cartilage-associated proteins type II collagen and Sox9 was up-regulated(P<0.05),and the expression of hypertrophy-associated proteins type X collagen and Runx2 was down-regulated after overexpression of nerve growth factor(P<0.05).(4)The results indicated that nerve growth factor could promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs. OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal. METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of"exercise,physical activity,methamphetamine,inhibitory function,craving,addiction"in Chinese and"sport*,exercise,methamphetamine,drug craving,executive function,addiction"in English.According to the inclusion and exclusion criteria,86 documents were finally included for review. RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain's ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain's reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain's nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.

This article is to illustrate the connection between neutrophil extracellular traps （NETs） and stasis-toxin interactions during the development of liver cancer， and to provide ideas for the prevention and treatment of liver cancer. It is believed that the mechanism of tumor-related thrombosis formation caused by NETs is closely related to "stasis" in traditional Chinese medicine （TCM）， and the continuous maintenance or enhancement of tumor microenvironment by NETs is closely related to "toxin" in TCM； the strong coagulation-promoting effect of NETs makes the local microenvironment， which can be regarded as the toxin caused by blood stasis； the changes of tumor microenvironment induced by NETs further induced platelet aggregation， which may present a state of stasis caused by toxin； the pathological changes of liver cancer caused by NETs can be regarded as the microscopic manifestation of the mechanism of stasis-toxin interaction of liver cancer.

Objective: To optimize the determination of pentachlorophenol in wooden chopping boards through pretreatment of miniaturized samples. Methods: The pretreated wooden chopping board samples were subjected to ultrasound extraction (1 mL of 0.5 mol/L K2CO3 added in 5 mL extraction solution) in 8 mL acetone and 2 mL water, followed by derivatization with 0.3 mL acetic anhydride, extraction with n-hexane and separation with DB-5ms column (30 m×0.25 mm, 0.25 μm). Gas chromatography tandem mass spectrometry (GC-MS/MS) was performed in multiple reaction monitoring (MRM) mode with quantitative analysis using the internal standard method. Results: The GC-MS/MS assay showed a good linear relationship within the range of 0.01 to 0.2 µg/mL (R2>0.999), with a 0.003 mg/kg limit of detection and 0.01 mg/kg limit of quantitation. The mean recovery rates were 84.2% to 96.7% at spiked concentrations of 0.003, 0.01 and 0.03 mg/kg, with relative standard deviation of 2.2% to 6.1%. Conclusions The established GC-MS/MS assay is easy to perform, environment-friendly, highly accurate and sensitivity, which is feasible for determination of pentachlorophenol in wooden chopping boards.

【Objective】 To investigate the effects of the loss of exon 1 of TFE3 on nuclear localization of chimeric TFE3 protein in TFE3 translocation renal cell carcinoma (TFE3 tRCC). 【Methods】 The localization of TFE3 protein in TFE3 tRCC and clear cell renal cell carcinoma (ccRCC) were detected with immunochemistry. The exon retention of TFE3 gene in TFE3 tRCC was analyzed in databases and literatures. The plasmids containing TFE3 full-length and different-length of TFE3 exons which were constructed to pCDH-MCS-EGFP-Puro were transfected into HEK293T using Lipo Fiter^TM. The localization of EGFP protein in HEK293T cells were detected with confocal microscopy. The localization of TFE3 protein and truncated TFE3 protein were detected with Western blotting. The mRNA expression of the downstream genes of TFE3 protein were detected with q-PCR. 【Results】 Strong nuclear signal of TFE3 protein was observed in TFE3 tRCC, whereas TFE3 protein in ccRCC was mainly localized in cytoplasm. The results of fluorescence imaging and Western blotting showed that TFE3 full-length protein was expressed both in nucleus and cytoplasm, and the expression of truncated TFE3 protein was mainly localized in nucleus. The q-PCR analysis demonstrated that the deletion of exon 1 in TFE3 gene led to a higher transcriptional level of targeted genes of TFE3 protein. 【Conclusion】 The loss of exon 1 in TFE3 played a critical role in preventing TFE3 protein from entering the nucleus. In TFE3 tRCC, the loss of exon 1 in TFE3 gene leads to the nuclear localization of TFE3 fusion protein and activation of its downstream target genes. This mechanism promises to uncover the occurrence and development of TFE3 tRCC.

Objective To study the effect of mitochondrial reactive oxygen species(ROS)on male fertility and its application value in assisted reproduction so as to provide a new method for fertility assessment and etiological treatment of male infertility.Methods The relationship between sperm ROS and male infertility,sperm nuclear DNA integrity and sperm membrane function was analyzed.Then the relationships of the ROS of sperms for fertiliza-tion with fertilization rate,cleavage rate,embryo rate and pregnancy outcome were analyzed.Results(1)The percentage of the high ROS in sperm membrane of the male infertility group was significantly higher than that of the normal fertility group(P<0.01),but there was no statistical difference in the percentage of the high ROS in the sperm mitochondria between the two groups.(2)The normal rate of sperm membrane function in the normal group was significantly higher than that in the abnormal group(P<0.01),but there was no significant difference in the sperm DNA fragmentation index(DFI)between the groups.(3)There was significant difference in the fertilization rate between the IVF control group and IVF observation group,but no significant difference was seen in the cleavage rate,excellent embryo rate and clinical pregnancy rate between the groups.Conclusion Sperm ROS is related to male fertility to some extent.Abnormal ROS may lead to impaired sperm membrane function and affect sperm fertilization ability,thus affecting male fertility.The detection of ROS in sperm can be used as a new method to evaluate male fertility and provide a basis for diagnosis or treatment of male infertility.For patients with ART or infertility,the appropriate time to conceive can be selected according to the sperm ROS level.

Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.

Objective:To explore the predictive value of preablative stimulated thyroglobulin (psTg) level before 131I treatment on the excellent response (ER) to 131I treatment in patients with functional residual lymph node metastasis without distant metastasis after papillary thyroid carcinoma (PTC) surgery. Methods:From March 2011 to June 2015, 72 patients (22 males, 50 females, age: 14-76 (46.5±14.4) years) who were diagnosed with functional lymph node metastasis without distant metastasis at the time of their first 131I treatment after total thyroid bilobectomy + lymph node dissection performed in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively included, and their serum thyroglobulin antibody (TgAb) levels were normal. Patients were divided into ER group and non-ER group according to the treatment response assessment system. Independent sample t test, χ2 test, and Mann-Whitney U test were used to compare the basic clinical characteristics between the two groups, and then multivariate logistic regression was performed. The ROC curve was employed to evaluate the predictive value of psTg and lymph node size in 131I treatment response. Results:The treatment responses of 44 patients were ER, and those of 28 were non-ER. The differences in gender, age, clinical stage, number and location of postoperative metastatic lymph nodes between ER and non-ER groups were not statistically significant ( t=0.82, χ2 values: 0.16-2.60, all P>0.05), while there were significant differences in American Thyroid Association (ATA) initial risk stratification ( χ2=33.38), lymph node size ( U=296.50) and psTg ( U=111.00, all P<0.001). PsTg (odds ratio ( OR)=0.047, 95% CI: 0.004-0.500, P=0.011) and lymph node size ( OR=0.146, 95% CI: 0.032-0.666, P=0.013) were independent factors affecting ER, whereas ATA initial risk stratification was not an independent factor ( OR=0.266, 95% CI: 0.051-1.390, P=0.116). AUCs for psTg and lymph node size were 0.904 and 0.873, respectively. The cut-off value of psTg was 20.05 μg/L with the sensitivity and specificity of 96.4%(27/28) and 75.0%(33/44) respectively, and lymph node size was 0.75 cm with the sensitivity and specificity of 78.6% (22/28) and 81.8% (36/44) respectively. Conclusion:PsTg can be used to predict 131I outcomes in patients with functional lymph node metastases after PTC, and lymph node size also has effect on ER.

Objective:To investigate the optimal monoenergetic level of virtual monoenergetic images (VMI) in transplanted renal artery on a dual-layer spectral detector CT.Methods:A retrospective study was performed on 16 renal transplant patients who underwent transplanted renal angiography on a dual-layer spectral detector CT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to April 2021. Conventional 120 kVp polyenergetic images (PI) were reconstructed, and virtual monoenergetic images (VMIs) in range of 40-200 keV with interval of 10 keV were reconstructed, too. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of 120 kVp PI and VMIs were measured. Meanwhile, the subjective scores of the display of transplanted renal artery were performed on volume rendering images of 120 kVp PI and VMIs. Spearman correlation analysis was used to explore the correlation between energy levels and SNR or CNR. Rank sum tests were performed to compare the parameters of image quality between the VMI which had the highest SNR and CNR, and the other VMIs, or 120 kVp PI.Results:Among the VMIs, SNR or CNR was negatively correlated with energy levels ( r =-0.86 and -0.88, all P<0.001). The SNR [22.80(18.57, 34.16)] and CNR [35.38(25.97, 39.01)] of 40 keV VMI were the highest, and significantly higher than that of 120 kVp PI and 50-200 keV VMIs, all the differences were statistically significant (all P<0.05). The subjective scores of 40 keV VMI and 120 kVp PI were 5 (5, 5) and 4 (3, 5), respectively. The score of 40 keV VMI was significantly higher than that of 120 kVp PI ( Z=-2.60, P=0.009). There were no significant differences in subjective scores between 40 keV VMI and 50-70 keV VMIs ( Z=-1.00, -1.41, -1.73, P=0.317, 0.157, 0.083), but the subjective score of 40 keV VMI was higher than that of 80-200 keV VMIs and the differences were statistically significant (all P<0.05). Conclusions:As for the images of transplanted renal angiography on a dual-layer spectral detector CT, the image quality of 40 keV VMI was best, thus 40 keV was the optimal monoenergetic level.